Drosophila Ube3a regulates monoamine synthesis by increasing GTP cyclohydrolase I activity via a non-ubiquitin ligase mechanism

Transient receptor potential vanilloid 1 (TRPV1) channels are involved in several inflammatory diseases. However, their action is still controversial, and both pro-inflammatory and anti-inflammatory roles have been described. We used a strain of TRPV1-KO mice to characterize the role of these channels in experimental autoimmune encephalomyelitis (EAE), which models multiple sclerosis (MS) in mice. EAE mice showed higher lethality in the peak phase of the disease and a better recovery of the surviving animals in the chronic stages, compared to their wild-type (WT) counterparts. By means of whole-cell patch clamp experiments in corticostriatal brain slices, we found that the absence of TRPV1 channels exacerbated the defect of glutamate transmission occurring in the peak phase of EAE, and attenuated the alterations of GABA synapses in the chronic phase of EAE, thus paralleling the dual effects of TRPV1-KO on the motor deficits of EAE mice. Furthermore, in slices from non-EAE mice, we found that genetic or pharmacological blockade of TRPV1 channels enhanced the synaptic effects of tumor necrosis factor α (TNF-α) on glutamate-mediated excitatory postsynaptic currents, and prevented the action of interleukin 1β (IL-1β) on GABAergic inhibitory postsynaptic currents. Together, our results suggest that TRPV1 channels contrast TNF-α-mediated synaptic deficits in the peak phase of EAE and, in the chronic stages, enhance IL-1β-induced GABAergic defects. The opposing interplay with the synaptic actions of the two major pro-inflammatory cytokines might explain the bimodal effects of TRPV1 ablation on the motor deficits of EAE, and suggests that the inflammatory milieu determines whether TRPV1 channels exert preferentially aversive or protective effects on neurons during neuroinflammatory diseases.     

Effects of socioeconomic position on inflammatory and hemostatic markers: a life-course analysis in the 1958 British birth cohort

The cumulative effects of socioeconomic position (SEP) on cardiovascular disease have been described, but the pathways are unclear. In this study, the authors examined the effects of life-course SEP on inflammatory and hemostatic markers: fibrinogen, C-reactive protein, von Willebrand factor antigen, and tissue plasminogen activator antigen. Data from the 1958 British birth cohort, including data on persons who underwent a biomedical follow-up in 2002-2004, were used. Social class was determined at three stages of respondents' lives: childhood (birth), early adulthood (age 23 years), and midlife (age 42 years). A cumulative indicator score of SEP was calculated that ranged from 0 (always in the highest social class) to 9 (always in the lowest social class). In men and women, associations were observed between cumulative indicator score and fibrinogen (p < 0.001), C-reactive protein (p < 0.001), von Willebrand factor antigen (p < or = 0.05), and tissue plasminogen activator antigen (p < 0.001 only in women). The trends in fibrinogen and C-reactive protein remained after adjustment for body mass index, smoking, and physical activity. However, the trends became nonsignificant for von Willebrand factor antigen and tissue plasminogen activator antigen in women. Risk exposure related to SEP accumulates across the life course and contributes to raised levels of fibrinogen and C-reactive protein, while childhood SEP influences hemostatic markers more than does adult SEP.     

Nitrate-induced Biochemical and Histopathological Changes in the Liver of Rats:Ameliorative Effect of Hyparrhenia hirta

Objective The present study investigated the protective role of Hyparrhenia hirta （H. hirta） against sodium nitrate （NaNO3）-induced hepatoxicity. Methods Male Wistar rats were randomly divided into three groups： a control group and two treated groups during 50 d with NaNO3 administered either alone in drinking water or co-administered with H. hit＇to. Results NaNO3 treatment induced a significant increase in serum levels of glucose, total cholesterol and triglyceride while serum total protein level decreased significantly. Transaminases and lactate deshydrogenase activities in serum were elevated indicating hepatic cells＇ damage after treatment with NaNO3. The hyperbilirubinemia and the increased serum gamma glutamyl transferase activities suggested the presence of cholestasis in NaNO3 exposed rats. In parallel, a significant increase in malondialdehyde level along with a concomitant decrease in total glutathione content and superoxide dismutase, catalase and glutathione peroxidase activities were observed in the liver after NaNO3 treatment. Furthermore, nitrate caused a significant induction of DNA fragmentation. These modifications in NaNO3-treated rats corresponded histologically with hepatoceltular necrosis and mononuclear cells infiltration. H. hirta supplementation showed a remarkable amelioration of the abnormalities cited above. Conclusion The results concluded that the treatment with H. hirta had a significant role in protecting the animals from nitrate-induced liver dysfunction.     

Significant heterogeneity in the geographical distribution of diffuse grade II/III gliomas in France

The recognition of stem cells (SC) in the adult CNS and in association with gliomas has spawned an entire field of research and intense investigation. A large body of knowledge is being accumulated to gain insight into the pathobiology of gliomas with the intent of finally improving the grave prognosis that continues to beset patients with high grade gliomas (HGG). In this article, we provide a historical overview of the events leading to the discovery of SC and glioma stem cells (GSC). We then focus on the current understanding of GSC with respect to markers, clinical significance, and their targeting. We discuss current data and developments using SC as vehicles to delivery therapeutic agents to HGG. We conclude with a discussion of opportunities for future development and concepts aimed at reducing tumor recurrence and improving survival for patients with HGG.     

Preparation of cellulosic Ag-nanocomposites using an ionic liquid

Cellulose-based nanocomposites have gained much attention due to their remarkable biological properties such as biodegradability, biocompatibility, and low toxicity. In this research work, 1-h-3-methylimidazolium hydrogen sulfate ionic liquid was employed as an efficient solvent for preparation of cellulosic Ag-nanocomposites (CRC/AgNPs composite) from Neem plant. Ionic liquid plays a dual role in obtaining cellulose-rich compound (CRC; removing lignin and hemicellulose components) and plant’s extract (phenolic compounds such as flavonoids, tannins, etc.) that reduces the AgNO₃ into AgNPs for preparation of CRC/AgNPs composite. The prepared CRC/AgNPs composite was characterized using XRD, FTIR and SEM techniques. The XRD and FTIR spectral analysis showed the characteristic peaks assigned to cellulosic constituent and AgNPs. SEM analysis revealed the particles in the range from 26 to 56 nm. The CRC/AgNPs composite was evaluated for its antibacterial and mechanical properties. The antibacterial activity against S. aureus and E. coli for CRC/AgNPs composite was observed in comparison to CRC. Cell viability and morphology were performed on MC3T3-E1 cells which showed no as such toxicity for the prepared CRC/AgNPs composite. Moreover, the addition of CRC/AgNPs composite as a filler increased the compression strength of polymeric materials.     

Prenatal Nicotine and CNS Development

The teratological effect of nicotine has been studied during different trimesters of pregnancy. Three groups of pregnant albino Swiss mice were used for each trimester. The daily doses of nicotine base used were equivalent to 10 (900 micrograms/kg), 20 (1,800 micrograms/kg), or 30 (2,700 micrograms/kg) cigarettes. The control groups were given normal saline. The drug and the saline solution were administered subcutaneously. The results showed that prenatal nicotine prolonged the latency and delayed the onset and extinction of audiogenic seizures in the offspring. These effects were more pronounced during the third trimester and particularly with the largest dose. These findings indicate that prenatal nicotine might delay the postnatal development of the CNS if it is given during the late stage of pregnancy.     

Coexistence of Leishmania tropica and Leishmania infantum in Sefrou province,Morocco

Cutaneous leishmaniasis (CL) has been recently emerged in new foci, posing a public health problem. Increasing cases of CL have been reported during recent years in Sefrou province, a previously non-endemic area. The present study was designed for epidemiological and parasitological characterization of the disease for the first time in this area. The results of a retrospective analysis of CL cases reports, between 2000 and 2011 showed that the incidence was estimated to 463/100,000 inhabitants/year, with a total of 1242 cases were notified from 1997 to 2011. Most patients were infected in the sector El Menzel (22.81%) and Sefrou (20.51%). Other cases have been reported in the 15 other sectors, reflecting the geographical spread of the disease. The highest rate lesions were found in the age group of 9 years or less with significant differences (p-value < 2.2e−16) comparing to the older age groups. The most affected lesion was localized in the face (64%). The average number of lesions per patient was 2.35 with a maximum of 5 lesions. The clinical aspects of lesions were mostly crusted. The causative agents of CL in this province were identified as the coexistence of L. tropica and L. infantum by species-specific ITS1-PCR-RFLP assay. CL remains an emergent disease in Sefrou with an incidence and a continuously geographical spread. Recent environmental changes, auspicious to vectors had probably contributed to that situation.